Exhaled Breath Analysis for Prediction of Response to Anti-PD1 Therapy in Patients with NSCLC

Rationale: Anti-PD1 therapy is effective in advanced NSCLC patients, however response rates are low (±20%). Therefore, efforts are ongoing to find a biomarker for prediction of response and early response monitoring. If properly validated, molecular profiling of exhaled air may qualify for this in patients treated with anti-PD1 therapy. Aim: To determine the accuracy of exhaled breath analysis at baseline and follow-up for assessing responders vs. non-responders to anti-PD1 treatment in NSCLC patients. Methods: This was an uncontrolled prospective intervention study in NSCLC patients. At baseline and 6 weeks follow-up breathprints were collected in duplicate by electronic nose (eNose: SpiroNose) [De Vries JBR 2015]. RECIST 1.1 criteria were used for response evaluation at three months and reported accordingly: Partial response (PR), stable disease (SD) and progressive disease (PD). Data analysis involved signal processing, ambient correction, and statistics based on principal component (PC) analysis, followed by discriminant analysis. Results: Exhaled breath data of 58 NSCLC patients with PD (n=33), SD (n=16) and PR (n=9) were available at baseline. PC4 showed a significant difference (p<0.01) between responders (PR and SD) and non-responders (PD) with an ROC-AUC of 0.84±0.05. At follow-up breath data of 36 NSCLC patients (PD:16, SD:14, PR:6) were collected. PC5 showed a significant difference (p=0.027) between responders and non-responders with an ROC-AUC of 0.86±0.05. Conclusion: Breath analysis by eNose allows discrimination between responders and non-responders to anti-PD1 treatment at baseline and 6 weeks follow-up and may therefore be of value to predict outcome and monitor NSCLC.